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Advanced pharmaceutical delivery via the use of targeting elements is an emerging research area with the potential to enhance the delivery of drug molecules to targeted sites. Conventional therapeutic delivery systems are significantly challenged by the inefficient delivery of a sufficient active drug dosage to maximize therapeutic effects on specific malignant sites, and this results in systemic cytotoxicity, low therapeutic indices, and adverse side effects. Aptamers are short and single-stranded RNA or DNA oligonucleotides with high binding affinity, sensitivity, and specificity toward their targets. They are generated from the systematic evolution of ligands by exponential enrichment assay which allows the isolation of aptamers for a wide range of targets including viruses, bacteria, cancer cells, ions, proteins, and tissues. Aptamers represent a new generation of targeting elements and have become paragons of affinity bionavigators to improve targeted drug delivery platforms by providing effective pharmacokinetics and pharmacodynamics. Aptamers have demonstrated to be promising therapeutic delivery agents and targeting elements by navigating active drug molecules specifically to, and into, target cells. Notwithstanding, the therapeutic efficacy of aptamers are challenged by weak endocytosis due to cell membrane repulsion, renal filtration, and endonuclease degradation. Delivery of aptamers in formulation with molecularly engineered biopolymers presents opportunities to minimize physicochemical challenges for effective delivery and enhanced therapeutic efficacy by providing a more controlled and prolonged drug release profile. This chapter provides an overview of the role of aptameric formulations in biopolymer colloids to enhance pharmaceutical delivery through improved drug encapsulation efficiency, loading capacity, in vivo half-life, targeted cellular uptake, drug release kinetics, and therapeutic effects.